Articular cartilage is one of a number of tissues in the body that bears load and slides relative to an apposing tissue surface with remarkable tribological properties -- low friction, low wear, and multiple modes of lubrication acting to lower friction and/or wear. However, in aging and osteoarthritis, the articular surface becomes roughened and eroded. Such deterioration may be the result of several factors leading to excessive loading, a failure in lubrication mechanisms, or both. The broad, long-term objectives are to contribute to the understanding of the mechanobiological system of the interacting joint compartments in order to gain insight into the mechanisms and consequences of lubrication of articular cartilage in joints. This proposal seeks to advance the understanding of lubrication mechanisms, in particular the molecular basis for boundary-mode lubrication of articular cartilage by synovial fluid. The overall hypothesis to be tested is that boundary lubrication of articular cartilage occurs via interactions of synovial fluid molecules with the articular surface, reducing boundary-mode friction and wear, and thereby contributing to the mechanical maintenance of healthy joints. This hypothesis suggests that the concentration of certain molecules within the joint cavity and their adherence at the articular surface are critical determinants of functional lubrication. The specific hypotheses to be tested are: Hypothesis 1: The SF components that lower friction at a cartilage-cartilage interface via boundary lubrication are Lub/SZP, SAPL, and HA, acting alone or in combination. Hypothesis 2: The SF components that lower wear at a cartilage-cartilage interface via boundary lubrication are Lub/SZP, SAPL, and HA, acting alone or in combination. Hypothesis 3: Solutions of biosynthetic and actual SF provide articular cartilage with friction and wear properties according to levels of Lub/SZP, SAPL, and HA, and results of the studies addressing Hypotheses 1 and 2. To address each hypothesis, studies are proposed beginning with tissue-level studies on excised osteochondral fragments in a cartilage-on-cartilage test configuration. They proceed to selected joint-scale biomechanical experiments on articulating cartilage. Relevance to Public Health: Confirmation of the above hypotheses is relevant both to the normal maintenance of joint health and to pathogenic processes in arthritic disease. Such information may ultimately facilitate diagnostic analysis and therapeutic manipulation of molecules of mechanical importance in the synovial fluid compartment. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
1R01AR051565-01A2
Application #
7147152
Study Section
Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Tyree, Bernadette
Project Start
2006-05-10
Project End
2011-02-28
Budget Start
2006-05-10
Budget End
2007-02-28
Support Year
1
Fiscal Year
2006
Total Cost
$339,809
Indirect Cost
Name
University of California San Diego
Department
Engineering (All Types)
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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